whoguidelines for the prevention and control of carbapenem

WHO Guidelines for the prevention and control of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in health care facilities

Prof. M. Lindsay Grayson, University of Melbourne, AustraliaSponsored by the World Health Organization

HostedbyAWebberTrainingTeleclasswww.webbertraining.com

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WHO Guidelinesfor the prevention and control of

carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and

Pseudomonas aeruginosa in health care facilities

Prof. M. Lindsay GraysonInfectious Diseases & Microbiology Department, Austin Health

Department of Medicine, University of Melbourne, Australia

Hosted by Prof. Shaheen MehtarStellenbosch University, Cape Town

Infection Control Africa Network (ICAN)

Sponsored by WHO InfectionPrevention and Control Global Unit

www.webbertraining.com November 13, 2017

22016

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• https://www.youtube.com/watch?v=LZapz2L6J1Q&feature=youtu.be

2016

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• Concern about the burden of illness associated with CRE-CRAB-CRPsA infection/colonisation = urgent priority

Rationale for CRE-CRAB-CRPsA Recommendations4




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• CRE-CRAB-CRPsA infection is associated with high morbidity and mortality

• CRE-CRAB-CRPsA transmission associated with high potential to cause outbreaks

• Key CR mechanism - a mobile resistance gene - readily transmitted between various intestinal bacterial species

Rationale for CRE-CRAB-CRPsA RecommendationsReasons

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• Long-term consequences of CRE-CRAB-CRPsA acquisition can be severe− Duration of colonisation and subsequent risk for infection can be long− Can have substantial psychological implications for colonised patients

• Current lack of effective treatments for infected and/or colonised patients


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• CRE-CRAB-CRPsA are highlighted as the top critical priority pathogens− WHO publication Prioritization of pathogens to guide discovery, research and

development of new antibiotics for drug-resistant bacterial infections


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• Cost impact of colonisation and infection with CRE-CRAB-CRPsA on healthcare systems is high− Potentially threatening the stability of health care systems in both the short and long term− IPC is critical to control these costs and resource implications


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• Cost impact of colonisation and infection with CRE-CRAB-CRPsA on healthcare systems is high− Potentially threatening the stability of health care systems in both the short and long term− IPC is critical to control these costs and resource implications


Note:• Prevention and control of CRE-CRAB-CRPsA

should be seen in the context of the broader priority to implement effective IPC for the prevention of all HAI and the strengthening of health care service delivery

• Importance of good antimicrobial stewardship -not included in these GLs, but critical

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l Dr. Benedetta Allegranzi

l Dr. Matthias Egger

Key staff 10




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• George L. Daikos (Laikon and Attikon Hospitals, Greece)• Petra Gastmeier (Charité Universitätsmedizin, Germany)• Neil Gupta (CDC, USA)• Ben Howden (University of Melbourne and Austin Health, Australia)• Bijie Hu (Chinese Infection Control Association, People’s Republic of China)• Kushlani Jayatilleke (Sri Jayewardenapura General Hospital, Sri Lanka)• Marimuthu Kalisvar (Tan Tock Seng Hospital and National University of Singapore)• Anna-Pelagia Magiorakos (European CDC, Sweden)• Shaheen Mehtar (Infection Control Africa Network; Stellenbosch University, South Africa)• Maria Luisa Moro (Agenzia Sanitaria e Sociale Regionale, Italy)• Babacar Ndoye (Infection Control Africa Network, Senegal)• Folasade Ogunsola (College of Medicine, University of Lagos, Nigeria)• Fernando Otaíza (Ministry of Health, Chile)• Pierre Parneix (Société Francaise d’Hygiène, Hôpital Pellegrin, France)• Mitchell J. Schwaber (National Center for Infection Control, Tel Aviv University, Israel)• Sharmila Sengupta (Medanta - The Medicity Hospital, India)• Wing-Hong Seto (WHO Collaborating Centre, Hong Kong, China)• Nalini Singh (Children's National Medical Center; George Washington University, USA)• Evelina Tacconelli (University Hospital Tübingen, Germany)• Maha Talaat (CDC Global Disease Detection Programme, Egypt)• Akeau Unahalekhaka (Chiang Mai University, Thailand).

Experts who served on the GDG 11

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WHO Region CRE CRAB CRPsAEPOC Non-

EPOCEPOC Non-

EPOCEPOC Non-

EPOC

Africa - - - - - -America 4 14 3 5 1 3Eastern Mediterranean

4 3 - - - -

Europe 2 17 10 1 5South-East Asia

- - - - - 1

Western Pacific

1 1 2 6 1 -

Total 11 35 5 21 3 9

Included studies according to WHO region

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Included studies according to study designsStudy design CRE CRAB CRPsA

EPOC Non-EPOC

EPOC Non-EPOC

EPOC Non-EPOC

Randomized controlled trials

- - - - - -

Non-randomized controlled trials

- - - - - -

Controlled before-after studies

- - - - - -

Interrupted time series 11 1 5 2 3 1

Before-after case counts

- 14 - 15 - 8

Longitudinal studies 2Mathematical modelling studies

- 3 - - - -

Non-controlled before-after studies

- 15 - 4 - -

Total 11 35 5 21 3 9

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Study scope/setting

CRE CRAB CRPsAEPOC Non-

EPOCEPOC Non-

EPOCEPOC Non-

EPOC

National 1 - - - - -Regional/State 1 1 - 1 - 1Hospital 6 12 2 8 1 3ICU 2 8 3 9 1 3Neonatal ICU - 2 - 2 - -Other Units: Haematology

- 8 - - 1 1

Other Units: Burns

- - - - - 1

LCTFs 1 4 - 1 - -Total 11 35 5 21 3 9

Included studies according to study scope/setting

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Study outcome CRE CRAB CRPsAEPOC Non-

EPOCEPOC Non-

EPOCEPOC Non-

EPOC

Incidence of infection 8 12 2 5 2 3Prevalence of infection 5 1Incidence of bloodstream infection

2 4 - 1 - -

Incidence of colonization 9 1 4 1 3Prevalence of colonization 1 13 - - - -

Incidence of “cases” (colonization or infection)

1 13 2 12 - 4

Total 11 35 5 21 3 9

Included studies according to study outcome

*Note: A number of studies reported multiple outcomes and are therefore listed more than once

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The panel recommends that multimodal IPC strategies should be implemented to prevent and control CRE-CRAB-CRPsAinfection or colonisation; and that these should consist of at least the following: •Hand hygiene •Surveillance (particularly for CRE)•Contact precautions: gowns, gloves, and patient isolation•Patient cohorting or single room isolation •Environmental cleaning

(Strong recommendation, very low to low quality of evidence)

Recommendation 1:Implementation of multimodal IPC strategies

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• Majority of studies from settings with a high prevalence of CRE-CRAB-CRPsA− But the IPC principles outlined were equally valid in all prevalence settings.

• Control of large outbreaks was recognized to be very costly− All studies were all undertaken in high- to middle-income countries− Concerns regarding cost implications of outbreaks and affordability in other settings.

Implementation of multimodal IPC strategiesKey Remarks

Recommendation 1: 24




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• Although the evidence = acute care facilities, similar IPC principles apply in all healthcare settings

• Implementing this REC-1 may be complex - requiring a multidisciplinary approach

• Good quality microbiological laboratory support is critical.





• Although the evidence = acute care facilities, similar IPC principles apply in all healthcare settings

• Implementing this REC-1 may be complex - requiring a multidisciplinary approach

• Good quality microbiological laboratory support is critical.

• Education/training and monitoring, audit and feedback are critical to make any multimodal strategy successful

• Daily patient bathing with chlorhexidine – insufficient evidence to be recommended






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The panel recommends that hand hygiene best practices according to the WHO Guidelines on hand hygiene in health care should be implemented.

(Strong recommendation, very low quality of evidence)

Recommendation 2:Importance of good hand hygiene compliance for

control of CRE-CRAB-CRPsA

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• As noted in the WHO “Guidelines on Core Components of Infection Prevention and Control Programmes at the National and Acute Health Care Facility Level”, hand hygiene compliance and consumption of alcohol-based hand-rub (ABHR) is very dependent on appropriate product placement and availability− Adequate resources are therefore necessary to ensure these features are met.

• Important to monitor hand hygiene compliance

• Beneficial impact of good hand hygiene compliance dependent on effective implementation strategies with local adaptation

Importance of good hand hygiene compliance for control of CRE-CRAB-CRPsA

Key Remarks





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The panel recommends that:

1. Surveillance of CRE-CRAB-CRPsA infection should be performed

2. Surveillance cultures for asymptomatic CRE colonization should be performed, guided by local epidemiology (outbreaks vs endemic settings) and risk assessment. – Populations to be considered for such surveillance include:

• Patients with previous CRE colonization• Patient contacts of CRE colonized/infected patients and • Patients with history of recent hospitalization in endemic CRE settings


Recommendation 3:Surveillance of CRE-CRAB-CRPsA infection and

surveillance cultures for asymptomatic CRE colonization

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• Surveillance (i.e. clinical monitoring and laboratory assessment of clinical samples) of CRE-CRAB-CRPsA infection is essential

• In some settings (e.g. LMICs) laboratory testing for carbapenem resistance among potential CRE-CRAB-CRPsA isolates may not be available or routine− Unanimous view - testing for carbapenem resistance in these pathogens should now be

considered as routine in all microbiology laboratories

Surveillance of CRE-CRAB-CRPsA infection(s)Key Remarks





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• Surveillance (i.e. clinical monitoring and laboratory assessment of clinical samples) of CRE-CRAB-CRPsA infection is essential

• In some settings (e.g. LMICs) laboratory testing for carbapenem resistance among potential CRE-CRAB-CRPsA isolates may not be available or routine− Unanimous view - testing for carbapenem resistance in these pathogens should now be

considered as routine in all microbiology laboratories

• Surveillance of CRE-CRAB-CRPsA infection needed to define the local epidemiology of these pathogens− Identify patterns− Better allocate resources to areas of need− Reviewing demographics, exposures, and locations of patients can help a facility

understand where, when, and which patients are getting sick to better prevent and control infections

Surveillance of CRE-CRAB-CRPsA infection(s)Key Remarks


• Information regarding a patient’s CRE colonization status does not (yet) constitute routine standard of care provided to patients by health systems− But information critical in an outbreak situation or high risk situations for CRE− Surveillance CRE culture results for colonization may not have immediate benefit to

the screened patient, but instead contribute to the overall IPC response to CRE− Information regarding CRE colonization status could potentially have important

beneficial effects on the antibiotic treatment plan for screened patients with subsequent CRE infection. impact of a CRE outbreak.

Surveillance cultures for asymptomatic CRE colonization

Key Remarks





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• Information regarding a patient’s CRE colonization status does not (yet) constitute routine standard of care provided to patients by health systems− But information critical in an outbreak situation or high risk situations for CRE− Surveillance CRE culture results for colonization may not have immediate benefit to

the screened patient, but instead contribute to the overall IPC response to CRE− Information regarding CRE colonization status could potentially have important

beneficial effects on the antibiotic treatment plan for screened patients with subsequent CRE infection.

• This recommendation should always apply in an outbreak situation (and also ideally in endemic settings)− Extensive discussion re. resource limitations (esp. LMICs) = prioritization of resources − No one single best surveillance approach - decision should be guided by the local

epidemiology, and likely clinical impact of a CRE outbreak.


Key Remarks


• Surveillance screening based on a patient risk assessment (i.e. higher risk of CRE acquisition, the potential risk posed to others in their environment). Categories to be considered: − Patients with a previously known history of CRE colonization or infection

− Epidemiologically-linked contacts of newly identified patients with CRE colonization or infection (this could include patients in the same room, unit or ward)

− Patients with a history of recent hospitalization in regions where the regional epidemiology of CRE suggests an increased risk of CRE acquisition (e.g. hospitalization in a facility with known or suspected CRE).

− Patients who, based on the epidemiology of their admission unit, may be at increased risk of CRE acquisition and infection (e.g. immunosuppressed patients, and those admitted to ICUs, transplantation services, or haematology units etc.)


Key Remarks





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• Surveillance cultures - feces best > rectal swab > perinanal swab− Minimum one culture necessary; >1 better

• Take surveillance as soon as possible after hospital admission or risk exposure− Prompt processing

• Optimal frequency of testing uncertain – commonly, on-admission, then weekly


Key Remarks


• Surveillance activities could involve potential harms or unintended consequences for the patient with ethical implications, including:

– A sense of cultural offensiveness or stigma associated with obtaining a rectal swab or providing a fecal specimen

– Potential discrimination of colonized or infected patients– HOWEVER – key mitigation measures are available and should be implemented


Additional Remarks





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Additional Remarks


• Ethical obligation to reduce the burden of CRE - larger public good • Ethical burdens associated with this:− personally identifiable information - risk of disclosure− discrimination − potential risks with rectal swabs− perhaps no direct benefit to patient

• Safeguards to be provided to protect the patients:− ongoing monitoring for ethical burden (discrimination, clinical harms), − making all patients aware of surveillance protocol to generate awareness− identification of vulnerable patients




• Insufficient evidence on surveillance cultures for CRAB and CRPsA colonization to extend the recommendation to these two microorganisms

– Sometimes beneficial - depends on the clinical setting, epidemiological stage (for example, outbreak) and body sites

– Optimal microbiological methods for CRAB-CRPsA surveillance cultures for colonization require further research

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Additional Remarks





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Contact precautions should be implemented when providing care for patients colonised or infected with CRE-CRAB-CRPsA


Recommendation 4:Contact precautions

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• “Contact precautions” = WHO definition of contact precautions – namely, the use of gowns, gloves, PPE, dedicated equipment, appropriate patient placement, limiting transport/movement of patients; use of disposable or dedicated patient-care equipment; and prioritizing cleaning and disinfection of patient rooms

• Contact precautions should be considered a standard of care for patients colonized or infected with CRE-CRAB-CRPsA in the vast majority of health systems

• HCW education regarding the principles of IPC and monitoring of contact precautions is crucial

Contact precautions Key Remarks





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• Pre-emptive isolation/cohorting and use of contact precautions may be necessary in some situations, until the results of surveillance cultures for CRE-CRAB-CRPsA are available

– Patients with a history of recent hospitalization in regions where the local epidemiology of CRE suggests an increased risk of CRE acquisition

• Clear communication regarding a patient’s colonization/infection status - important






• Pre-emptive isolation/cohorting and use of contact precautions may be necessary in some situations, until the results of surveillance cultures for CRE-CRAB-CRPsA are available

– Patients with a history of recent hospitalization in regions where the local epidemiology of CRE suggests an increased risk of CRE acquisition

• Clear communication regarding a patient’s colonization/infection status - important



• Inform patients of need for PPE practices to facilitate acceptance• Ethical burdens associated with this:− Reduced contact with health care providers− Discrimination − Resource constraints in material resource leading to poor management of patients

• Safeguards to be provided to protect the patients:− Active engagement of patients in the contact precaution decision− ? Patients under contact precautions receive priority services to mitigate potential harms




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Patients colonised or infected with CRE-CRAB-CRPsA should be physically separated from non-colonised/infected patients using:1) single room isolation, or2) cohorting with patients with the same resistant pathogen.


Recommendation 5:Patient Isolation

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• Inconsistent use of the terms “isolation” and “cohorting.” Standard definition used:− Isolation: Patients should be placed in single-patient rooms (preferably with own toilet

facilities) when available. When single-patient rooms are in short supply - cohort− Cohorting: Grouping together patients who are colonized or infected with the same

organism to confine their care to one area and prevent contact with other patients

• Purpose of isolation – to separate colonized/infected patients from non-colonized/non-infected patients

• Strongest evidence for CRE colonization/infection– But also likely to be effective for CRAB and/or CRPsA

• Patient isolation = some potentially negative unintended consequences– But that these can be minimized so as to outweigh these concerns

• Patient isolation - should always apply in an outbreak situation

Patient IsolationKey Remarks 1





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• Inconsistent use of the terms “isolation” and “cohorting.” Standard definition used:− Isolation: Patients should be placed in single-patient rooms (preferably with own toilet

facilities) when available. When single-patient rooms are in short supply - cohort− Cohorting: Grouping together patients who are colonized or infected with the same

organism to confine their care to one area and prevent contact with other patients

• Purpose of isolation – to separate colonized/infected patients from non-colonized/non-infected patients

• Strongest evidence for CRE colonization/infection– But also likely to be effective for CRAB and/or CRPsA

• Patient isolation = some potentially negative unintended consequences– But that these can be minimized so as to outweigh these concerns

• Patient isolation - should always apply in an outbreak situation



• Inform patients of need for isolation to facilitate acceptance• Ethical burdens associated with this:− Reduced contact with health care providers− Discrimination − Resource constraints in material resource leading to poor management of patients− Depression/ anxiety in the patient

• Safeguards to be provided to protect the patients:− Active engagement of patients in the isolation decision; psychological support− ? Patients under contact precautions receive priority services to mitigate potential harms

• Single rooms may not be possible in endemic situations– Particularly in low-income settings where resources and facilities are limited

• Some evidence to support the use of dedicated health care workers to exclusively manage isolated/cohorted patients

– Although there may be some feasibility issues






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Compliance with environmental cleaning protocols of the immediate surrounding area (i.e. “patient zone”) of patients colonised or infected with CRE-CRAB-CRPsA should be ensured


Recommendation 6:Environmental Cleaning

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• The“patient zone” = the patient and his/her immediate surroundings− Includes all inanimate surfaces that are touched by or in direct physical contact with the

patient such as the bed rails, bedside table, bed linen, infusion tubing bedpans, urinals and other medical equipment.

− Contamination is likely in toilets and items found nearby

• The optimal cleaning agent for environmental cleaning protocols for CRE-CRAB-CRPsA has not yet been defined– A number (n=3) studies used hypochlorite (gen. a concentration of 1000 ppm)

Environmental CleaningKey Remarks





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• The“patient zone” = the patient and his/her immediate surroundings− Includes all inanimate surfaces that are touched by or in direct physical contact with the

patient such as the bed rails, bedside table, bed linen, infusion tubing bedpans, urinals and other medical equipment.

− Contamination is likely in toilets and items found nearby

• The optimal cleaning agent for environmental cleaning protocols for CRE-CRAB-CRPsA has not yet been defined– A number (n=3) studies used hypochlorite (gen. a concentration of 1000 ppm)

• Educational programs for hospital cleaning staff – crucial– Multimodal strategies to implement environmental cleaning essential – including

institutional policies, structured education, monitoring compliance with protocols

• Assessment of cleaning efficacy by performing environmental screening cultures -worthwhile in some settings

• In some outbreak situations, temporary ward closures necessary to allow for enhanced cleaning

Environmental CleaningKey Remarks



Surveillance cultures of the environment for CRE, CRAB, and CRPsA may be considered when epidemiologically indicated

(Conditional recommendation, very low quality of evidence)

Recommendation 7:Surveillance cultures of the environment for CRE-

CRAB-CRPsA colonization/contamination

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• Correlation of environmental surveillance culture results to the rates of patient colonization/infection with CRE-CRAB-CRPsA should be undertaken with caution and depend on an understanding of the local epidemiology and resources

• Based on expert opinion (and only limited available data), surveillance cultures of the general environment were considered most relevant to CRAB outbreaks

• Outbreaks of CRPsA colonization/infection - more commonly associated with environmental CRPsA contamination involving water and waste-water systems such as sinks and faucets

Surveillance cultures of the environment for CRE-CRAB-CRPsA colonization/contamination

Key Remarks


The panel recommends:Monitoring of the implementation of multimodal strategies and feedback of results to health care workers and decision-makers


Recommendation 8:Monitoring, Audit and Feedback

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• Monitoring, audit and feedback of IPC interventions - fundamental component of any effective intervention - esp. for CRE-CRAB-CRPsA

• Appropriate training of HCWs who undertake monitoring – crucial– Is a key component of all IPC educational programs

• All components of the multimodal strategy intervention should be regularly monitored, including hand hygiene compliance

• Monitoring, audit and feedback of multimodal strategies are a key component of all IPC educational programmes

• IPC monitoring should encourage improvement and promote learning in a non-punitive institutional manner

Monitoring, Audit and FeedbackKey Remarks


Planned dissemination and implementationof the Guidelines

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• New CRE-CRAB-CRPsA Guidelines now available

• IPC interventions – the key to controlling CRE-CRAB-CRPsA in healthcare settings

• Implementation will be a challenge, but is necessary

Conclusions

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THANK YOU!

Help WHO highlight the role of IPC to combat AMRand participate in the World Antibiotic Awareness Week!

Learn more about WHO’s IPC work at:http://www.who.int/infection-prevention/en/

WAAW website: http://www.who.int/campaigns/world-antibiotic-awareness-week/en/

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